A comparative study of neuronal and inducible nitric oxide synthases: Generation of nitric oxide, superoxide, and hydrogen peroxide

Nitric oxide synthases (NOS) independent of the isozyme, produce nitric oxide ((NO)-N-.), superoxide (O-2(.-)), and hydrogen peroxide (H2O2). Since (NO)-N-. has been implicated in many physiological processes, the importance of O-2(.-) and H2O2 in regulating cell signaling by 'NO cannot be overlooked. Before addressing these questions, we investigated the production of (NO)-N-., O-2(.-), and H2O2 by purified NOS. NOS 1 and NOS 2 were chosen, as the flux of 'NO from each isozyme supports differential biological activity. We found that the initial rate and sustained production of 'NO was considerably greater for NOS 2 as compared to NOS 1. In the absence of L-arginine, however, NOS 1 generation of O-2(.-) and H2O2 was found to be substantially greater than that measured for NOS 2. Differences between NOS I and NOS 2 production of (NO)-N-., O-2(.-), and H2O2 may define the specific physiologic function of each isozyme. (c) 2005 Elsevier B.V. All rights reserved.